To the Editor:
Hybrid peripheral nerve sheath tumors have been reported uncommonly in the literature. They mainly include neurofibroma-schwannoma, schwannoma-perineurioma, neurofibroma-perineurioma, and granular cell tumor-perineurioma.1-4 They usually occur in young adults and most cases are not related to neurofibromatosis, although their occurrence during childhood and their association to neurofibromatosis have been documented.5,6
Early reports on hybrid peripheral nerve sheath tumors included biphasic neurofibroma-schwannoma and schwannoma-perineurioma examples, in which the 2 different components had abrupt boundaries, and thus were easily discernible on sections stained with hematoxylin and eosin.1,6,7 Kasakov et al were the first to report a case of hybrid peripheral nerve sheath tumor (interpreted as neurofibroma-perineurioma) in which both components were so intimately associated, in such a way that the neoplasm appear to have a monophasic pattern of growth on the hematoxylin and eosin stained sections: and only immunostains were able to depict its dual cell population.2 Later on, Shelekhova et al reported an additional case (interpreted as neurofibroma-perineurioma) also situated in the sub-cutaneous tissue.8 Recently, Hornick et al published a large series of cases with similar monophasic histological features as those reported by Shlekhova et al and Kasakov et al, but Hornick et al interpreted these lesions as hybrid schwannoma-perineuriomas.5 In Hornick et al series (except for the cases situated in viscera and skeletal muscle), all tumors were centered in the subcutaneous tissue in a wide anatomic distribution, whereas a minority of them also extended to the dermis. To the best of our knowledge, pure cutaneous monophasic hybrid peripheral tumors have not been reported so far.
Herein we report an example of a neoplasm, which, except for its dermal location, is indistinguishable from the previous reported monophasic schwannoma-perineurioma (or neurofibroma-perineurioma).
An 11-year-old boy came to medical attention complaining of a lump in the dorsal aspect of his right foot. The lesion had been present for around 3 years. As it grew slowly and progressively, his mother decided to search for medical assistance. No stigmata of neurofibromatosis were detected. It was surgically removed and has not recurred after an 18-month follow-up.
Macroscopically, the lesions consisted of a whitish, firm, 2.3 × 2.0 × 1.3 cm mass localized in the skin. Under a conventional microscope, the lesion showed a dermal based, exophytic lesion (Fig. 1), which was nonencapsulated. The overlying epidermis had slight psoriasiform hyperplasia and the underlying subcutaneous tissue was uninvolved (Fig. 2A, B). The neoplastic cells were embedded in a collagenous stroma, and were arranged in a somewhat diffuse storiform pattern, but in areas a lamellar pattern of growth was observed, and scattered whorls were also seen (Fig. 2C). In other fields, the neoplasm permeated dermal adnexae and periadnexal fat (Figs. 2D, 3A). The neoplasm was composed of 2 spindle cell populations, including cells with slender nuclei and bipolar cytoplasmic processes (perineurial component), and cells containing plumper nuclei and pale cytoplasm (schwannian component; Fig. 3B). Both cell populations were found intermixed throughout the lesion conferring a monophasic histologic pattern to the lesion. Scarce multinucleated and degenerated cells with hyperchromatic nuclei were found (Fig. 3B). Only one typical mitotic figure was found. No necrosis was identified.
Immunohistochemistry showed that the spindle cells diffusely expressed CD34, S-100 protein, and EMA (Fig. 3D, E). They were negative for melan-A, HMB-45, factor XIIIa, smooth muscle actin, desmin, CD31, and AE1/AE 3. The multinucleated giant cells had the same immunoprofile. No axons intermixed with the lesional cells were detected by neurofilament stain. Our final diagnosis: monophasic hybrid schwannoma-perinerioma.
Although some authors interpret the schwannian component of monophasic hybrid peripheral nerve sheath tumors as part of a neurofibroma (even though accepting that a schwanian component could be present in these areas);2 Hornick et al believe that the nonperineurial component is more related to schwannoma because the S-100 protein-positive cells in these tumors are as large as in schwannoma (whereas neurofibroma usually harbors smaller Schwann cells), there is not a clear-cut fibroblastic population (CD34 seems to stain only perineurial cells), and because of the absence or scarcity of axons in these tumors.5
However, regardless of one's individual preference about calling these neoplasms hybrid schwannoma-perineurioma or hybrid neurofibroma-perineurioma, the importance of recognizing this entity restricted to the dermis resides in avoiding mistaking it for more aggressive lesions such as dermatofibrosarcoma protuberans (DFSP) and desmoplastic/neurotropic melanoma. Indeed, the current case had storiform pattern of growth, diffuse CD34 expression, and showed infiltration of periadnexal adipocytes which are features worrisome for DFSP. Clues to the correct diagnosis include occasional perivascular cell whorling and diffuse expression of S-100 protein and EMA. Similarly, although our case had features reminiscent of desmoplastic melanoma, including S-100 protein expression and no melan-A and HMB-45 expression other features could rule-out this diagnosis, including absence of chronic inflammatory infiltrate permeating the neoplastic cells and diffuse expression of EMA. The current case should also be differentiated from neurofibroma containing floret-like giant cells which is frequently associated to neurofibromatosis type 1.9 The giant cells in such neurofibromas do not have smudged chromatine and are CD34?, whereas the giant cells observed in hybrid schwannoma-perineuriomas are schwannian in nature and harbor degenerative features. Finally, because of the hypercellular areas, storiform pattern, and the expression of CD34, our case may be reminiscent of cellular digital fibromas. The later entity, in contrast to hybrid schwannoma-perineurioma, does not express EMA and seems not to extend to the deep dermis.10
Alessandra C. Macarenco, MD
Dermis-Clinica Dermatologica, Sao Jose dos Campos, SP, Brazil
Ricardo S. Macarenco, MD
CIPAX-Medicina Diagnostica, Sao Jose dos Campos, SP, Brazil
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2. Kazakov DV, Pitha J, Sima R, et al. Hybrid peripheral nerve sheath tumors: schwannoma-perineurioma and neurofibroma-perineurioma. A report of three cases in extradigital locations. Ann Diagn Pathol
3. Zarineh A, Rabkin MS.Perineuriomas containing granular cells: 2 distinct variants? Am J Dermatopathol
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6. Zamecnik M, Michal M. Perineurial cell differentiation in neurofibromas. Report of eight cases including a case with composite perineurioma-neurofibroma features. Pathol Res Pract
7. Michal M, Kazakov DV, Belousova I, et al. A benign neoplasm with histopathological features of both schwannoma and retiform perineurioma (benign schwannoma-perineurioma): a report of six cases of a distinctive soft tissue tumor with a predilection for the fingers. Virchows Arch
8. Shelekhova KV, Danilova AB, Michal M, et al. Hybrid neurofibroma-perineurioma: an additional example of an extradigital tumor. Ann Diagn Pathol
9. Swick BL. Floret-like multinucleated giant cells in aneurofibromatosis type 1-associatedneurofibroma. Am J Dermatopathol
10. McNiff JM, Subtil A, Cowper SE, et al. Cellular digital fibromas: distinctive CD34-positive lesions that may mimic dermatofibrosarcoma protuberans. J Cutan Pathol